(M1030-09-56) Personalized 3D-Printed Tablets for Diabetes and Related Complications: Design, Optimization, and Evaluation

Purpose: The purpose of this study was to develop personalized 3D-printed bilayer tablets using Direct Powder Extrusion (DPE) technology for the simultaneous delivery of Metformin HCl (extended release) and Atorvastatin Calcium Trihydrate (immediate release). This approach aimed to improve medication adherence and therapeutic outcomes in diabetic patients with associated cardiovascular complications.

Methods: Pneumatic-based thermoplastic 3D printing was employed to fabricate bilayer tablets combining two Biopharmaceutical Classification System (BCS) model drugs. Eudragit RSPO was used as an extended-release polymer for Metformin HCl, and PEO N10 was employed for immediate release of Atorvastatin Calcium. The formulations were optimized for printability, mechanical integrity, and drug release using excipients such as PEG 3350, Pluronic F127, and sorbitol. The tablets were evaluated for physical characteristics, thermal behavior (DSC), crystallinity (XRPD), molecular interactions (FTIR), surface morphology (SEM), drug content (assay and HPLC), and in vitro drug release. Mass spectrometry was used to confirm the chemical integrity of the APIs post-printing.

Results: The optimized Metformin formulation (MET-7) achieved extended drug release, reaching 89.71% at 10 hours and meeting USP specifications. The Atorvastatin formulation (ACT-11) released 89.54% of the drug within 30 minutes, confirming suitability for immediate release. XRPD and DSC analyses indicated partial amorphization of Atorvastatin during printing, enhancing solubility, while FTIR showed no drug–excipient interactions. SEM analysis  revealed well-layered structures with consistent morphology. All formulations met USP requirements for assay and content uniformity, and mass spectrometry confirmed chemical stability of both drugs post-printing.

Conclusion: The study demonstrates the feasibility of using pneumatic-based DPE 3D printing to fabricate bilayer tablets with distinct release profiles, combining Metformin and Atorvastatin in a single dosage form. This single-step, solvent-free printing method enables personalized drug delivery, reduces pill burden, and offers a promising platform for producing polypills targeting chronic conditions such as diabetes and cardiovascular disease.

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Table 1 and Table 2 display the composition (% w/w) of Metformin HCl and Atorvastatin Calcium trihydrate 3D-printed tablets, respectively, with various excipients and formulation codes.

Top left: Schematic workflow illustrating the process from physical mixture preparation to pneumatic 3D printing and resulting bilayer 3D-printed tablet. Top right: Photographs of 3D-printed tablets: (a) Top view and (b) side view of a bilayer tablet composed of 100% infill MET-7 and 25% infill ACT-11 formulations. Middle: SEM images showing surface and cross-sectional morphology of Atorvastatin Calcium trihydrate, physical mixture, tablet formulation, and 3D-printed tablets. Bottom right: Dimensional measurements and top/side views of 3D-printed ACT-11 (top row) and MET-7 (bottom row) tablets, demonstrating size and shape uniformity.

Spectral and thermal analysis of tablet formulations: FTIR spectra, DSC thermograms, and pXRD diffractograms compare physical mixtures, pure drugs, and 3D-printed tablets to assess drug-excipient interactions and crystallinity.